The present invention is directed to the treatment of psoriasis using topical retinoids.
The retinoids are a family of compounds including vitamin A, retinoic acid (RA), related derivatives of these, and other compounds capable of binding to retinoic acid receptors (RAR). RA, which is a natural metabolite of vitamin A (retinol), is known as a potent modulator (i.e., an inhibitor or, to the contrary, a stimulator, depending on the nature of the cells treated) of the differentiation and proliferation of many normal or transformed cell types. All-trans-RA (tretinoin) acts on the differentiation and proliferation of cells by interacting with RARs contained in the cell nucleus. There are, to date, three identified subtypes of known RAR receptors, respectively termed RAR-.alpha., -.beta., -.gamma.. These receptors, after binding the RA ligand. interact with the promoter region of genes regulated by RA at specific response elements. To bind to the response elements, the RARs heterodimerize with another type of receptor designated as RXR. The natural ligand of RXRs is 9-cis-retinoic acid.
Many retinoids are known and have been described to date. Generally, retinoids can be identified by their ability to bind RARs, either as all the RARs or selectively to an individual RAR class. Further, retinoids exhibit a diverse spectrum of activities. Among these is use as a topical therapeutic for treatment of skin conditions.
There is presently in use an FDA approved treatment for psoriasis employing tazarotene topical gel that is marketed by Allergan, Inc. under the brand name Tazorac.TM.. Moreover, tretinoin, also known by the tradename Retin-A.TM., and adapalene are approved for topical use to treat skin conditions.
The mechanism of action in the treatment of psoriasis with tazarotene or other retinoids is not known. The current FDA-approved therapeutic regimen requires Tazorac.TM. gel to be applied topically in its 0.05% or its 0.1% formulation and left on the affected skin for long periods of time, e.g. overnight. It is generally applied in the evening and left in place until routine washing in the morning. Thus, in the treatment of psoriasis, the Tazorac.TM. gel would typically be left on the skin for 8 to 12 hours.
Unfortunately, a major shortcoming of this course of treatment is that adverse skin reactions are experienced by a significant portion of users. These reactions include pruritus, burning/stinging and erythema (sometimes severe), actual worsening of psoriasis, irritation and skin pain. Since the treatment regimen is usually prolonged, covering many weeks or months, any adverse reactions are rendered even more substantial in the perception of the user, often resulting in the interruption or abandonment of the treatment regimen. Thus the adverse reactions are not merely significant in-and-of themselves, but can make treatment ineffectual due to the inability or unwillingness of the user to follow the regimen.
To overcome these shortcomings, it has now been found that topically-applied retinoids can be used to treat psoriasis using a short-contact treatment regimen. For example. tazarotene has been used for short-contact therapy to treat psoriasis as disclosed in co-pending application entitled "Short Contact Treatment of Psoriasis with Tazarotene Compositions," filed on the same day as this application by the same inventors and which is hereby incorporated herein by reference.